Dimethyl Fumarate Modulates Oxidative Stress and Inflammation in Organs After Sepsis in Rats
Dimethyl Fumarate Modulates Oxidative Stress and Inflammation in Organs After Sepsis in Rats
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DOI：
10.1007/s10753-017-0689-z
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发表时间：
2018-02-01
期刊：
影响因子：
5.1
通讯作者：
Petronilho, Fabricia
中科院分区：
文献类型：
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作者：
Della Giustina, Amanda;Bonfante, Sandra;Petronilho, Fabricia
败血症被定义为由宿主对感染病原体的反应中断引起的危及生命的器官功能障碍。有证据表明氧化应激与脓毒症的进展有内在联系。富马酸二甲酯（DMF）是一种新型抗氧化口服治疗剂，它通过激活核因子红系2 （NFE2）相关因子2 （Nrf2）发挥保护作用。因此，本研究的目的是评估DMF在脓毒症动物模型大鼠不同器官中的作用。采用盲肠结扎穿刺法（CLP）治疗成年雄性Wistar大鼠脓毒症，假手术大鼠为对照组。实验组分为sham + vehicle、sham + DMF、sham + NAC、CLP + vehicle、CLP + DMF、CLP + NAC。大鼠分别于术后即刻和术后12 h灌胃DMF，术后3、6、12 h灌胃NAC （s.c）。脓毒症诱导24小时后，评估心脏、肝脏、肺和肾脏的中性粒细胞浸润、亚硝酸盐/硝酸盐浓度、脂质和蛋白质的氧化损伤、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性。脓毒症动物表现为中性粒细胞浸润、NO代谢增加、脂质和蛋白质氧化损伤增加、SOD和CAT活性降低，主要表现在心脏、肝脏和肺部，而dmf处理动物中性粒细胞浸润、NO代谢和氧化损伤显著减少，SOD和CAT活性升高。DMF对脓毒症诱导后24 h的氧化应激和炎症反应有明显的预防作用。
Sepsis is defined as life-threatening organ dysfunction induced by a disrupted host response to infecting pathogens. Evidences suggest that oxidative stress is intrinsically related to sepsis progression. Dimethyl fumarate (DMF) is a novel oral therapeutic agent with anti-oxidant properties which exerts protective effects through activation of nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2). Thus, the aim of this study is to evaluate the effect of DMF in different organs of rats submitted to an animal model of sepsis. Adult male Wistar rats were subjected to sepsis by cecal ligation and puncture (CLP) procedure and sham-operated rats was considered control group. The experimental groups were divided into sham + vehicle, sham + DMF, sham + NAC, CLP + vehicle, CLP + DMF, and CLP + NAC. Rats were treated by oral gavage with DMF immediately after and 12 h after surgery, or NAC (s.c.) at 3, 6, and 12 h after surgery. Twenty-four hours after sepsis induction, neutrophil infiltration, nitrite/nitrate concentrations, oxidative damage to lipids and proteins, superoxide dismutase (SOD), and catalase (CAT) activities were evaluated in the heart, liver, lung, and kidney. Septic animals presented increased neutrophil infiltration, NO metabolism, oxidative damage to lipids and proteins, and decreases of SOD and CAT activities, mainly in the heart, liver, and lung, while DMF-treated animals showed significant reduction in neutrophil infiltration, NO metabolism, and oxidative damage followed by increased SOD and CAT activities. DMF is effective in preventing oxidative stress and inflammation in rats 24 h after sepsis induction.